Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells. Issue 2 (2nd January 2019)

• Record Type: Journal Article
• Authors: Mei, Liangwei; Sang, Wenhua; Cui, Kai; Zhang, Yabin; Chen, Fuchun; Li, Xiaochun
• Is Part Of: Cancer science. Volume 110:Issue 2(2019)
• Page Start: 582
• Page End: 595
• Publication Date: 2019-01-02
• Subjects: apoptosis -- autophagy -- c‐Met -- norcantharidin -- osteosarcoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13900
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. The aim of the present study was to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppress the migration and invasion, decrease the colony‐forming ability and induce S phase cell cycle arrest of OS cells in a dose‐dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum stress and c‐Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These results provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS. Abstract : Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. The poor response to chemotherapy remains a critical factor for OS patients. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. Our results provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS.